The intravenous injection of F1 hybrid mice on the C57BL/10 background with parental spleen cells resulted in a loss in the ability of the F1 mice to generate T-cell mediated cytotoxic responses in vitro to TNP-self and alloantigens. The total abolition of response potential occurred within 4 days of injection, persisted for at least three weeks, and could be induced with as few as 2 times 10 to the 6th power spleen cells. The loss of response potential depended on the H-2 type of the parental cells, since H-2(k,a) spleen cells induced unresponsiveness, whereas H-2b spleen cells did not. The phenomenon may be: a) Strain-specific (possibly depending on the C57BL/10 genetic background) since (AKR crossed with DBA/2)F1 mice injected with parental cells did not exhibit the loss of immune potential; and b) dependent on a reaction against F1 alloantigens by grafted parental cells (GVH), since loss of immune activity was associated with enlarged F1 host spleens.